Reproducibility and transferability of topological data: experimental charge density study of two modifications ofl-alanyl-l-tyrosyl-l-alanine

Abstract

Two crystalline modifications of the tripeptide L-Ala-L-Tyr-L-Ala, which have different solvent molecules in the crystal structure (water and ethanol for modifications 1 and 2), were the subject of experimental charge density studies based on high resolution X-ray data collected at ultra-low temperatures of 9 K (1) and 20 K (2), respectively. The molecular structures and the intermolecular interactions were found to be rather similar in the two crystal lattices, so that this study allowed the reproducibility of the charge density of a given molecule in different (but widely comparable) crystalline environments to be examined. With respect to bond topological and atomic properties, the agreement between the two modifications of the title tripeptide was in the same range as found from the comparison with the previously reported results of tri-L-alanine. It follows that the reproducibility and transferability of quantitative topological data are comparable and that within the accuracy of experimental charge density work the replacement of the central amino acid residue L-Ala by L-Tyr has no significant influence, neither on bond nor on the atomic properties of the oligopeptide main chain. Intermolecular interactions in the form of hydrogen bonds were characterized quantitatively and qualitatively by topological criteria and by mapping the charge density distribution on the Hirshfeld surface.

Charge Density of L-Alanyl-glycyl-L-alanine Based on X-Ray Data Collection Periods from 4 to 130 Hours

“…'s of the three data sets of 0.4Å 3 for V tot , 0.4Å 3 for V 001 and 0.1 e for Q. Again these quantities are in line with the reproducibility we found in our earlier study on two modifications of Ala-Tyr-Ala and with several literature studies, where quantitative data of this type were compared [10].…”

“…Also no preference for one of the data sets can be found. Table 4 shows that for the bonds in the peptide bond region, if averaged over the three experiments (hence 6 data per entry), the bond topological properties compare very well with the corresponding averages recently reported for the Ala-Xxx-Ala class of compounds [10].…”

“…If we average over the 14 σ n values we get mean values of 0.069 eÅ −3 for the electron density and 3.4 eÅ −5 for the Laplacians. These quantities are in the same range as reported in the literature for the reproducibility of these topological descriptors [10] and the uncertainty range is that given by several authors [12 -14] to be considered if electron density results from different experiments are to be compared.…”

“…We have addressed this question in a further comparative charge density study in the oligopeptide field, in that tripeptides of the type L-Ala-Xxx-L-Ala were considered, where Xxx was to be varied among the 20 naturally occurring amino acids. Two studies of that type have been published recently, one with Xxx = L-Ala [9] and the second one on two modifications with Xxx = L-Tyr [10].…”

The active site of hen egg-white lysozyme: flexibility and chemical bonding

“…Topological properties of static electron densities are usually interpreted according to the quantum theory of atoms in molecules (QTAIM; Bader, 1994). This method has been extensively applied to crystals of amino acids and small peptides, especially tripeptides (Jelsch et al, 1998;Destro et al, 2000;Flaig et al, 2002;Rö del, 2003;Scheins et al, 2004;Dittrich et al, 2005;Mebs et al, 2006;Checiń ska et al, 2006;Kalinowski et al, 2007;Johnas et al, 2009). As opposed to static electron densities, dynamic electron densities employ both the atomic coordinates and the atomic displacements resulting from a structure refinement against diffraction data.…”